A program of research is proposed which involves the construction of an extensive and diverse set of myeloma-spleen cell hybrids which secrete monoclonal antibodies to human cell surface antigens. Hybrids will be generated by fusing spleen cells from mice immunized with human peripheral blood lymphocytes to the nonsecreting myeloma cell line P3-NS1-AG4-1. The monoclonal antibodies produced by cloned hybrid lines will be subjected to a program of screening designed to identify hybrids and producing antibodies to the surface antigens of human lymphocytes. Studies are outlined which will determine a) which of the monoclonal antibodies derived may be used as specific labels to identify subsets of human lymphocytes and b) as specific probes to identify functional populations of human lymphocytes. It is expected that an extensive "library" of monoclonal antibodies of the sort outlined would be generated and characterized during the proposed period of support. Highly specific, high titer monoclonal antibodies to lymphocyte surface antigens would extend our ability to detect and quantitate changes in B and T cell populations. They would also contribute decisively to the analysis of the roles played by various human lymphocyte subpopulations. It should also be pointed out that monoclonal antibodies to human cell surface antigens will find application in studies of the somatic cell genetics of the human. Such reagents can be used to establish the presence of a particular chromosome or chromosome segment in segregating human-rodent hybrids. They will also facilitate quantitative studies of the factors that regulate the expression of surface antigens in human cells.